M Channels Containing KCNQ2 Subunits Modulate Norepinephrine, Aspartate, and GABA Release from Hippocampal Nerve Terminals

Maria Martire, Pasqualina Castaldo, Monia D'Amico, Paolo Preziosi, Lucio Annunziato, Maurizio Taglialatela

Research output: Contribution to journalArticlepeer-review


KCNQ subunits encode for the M current (IKM), a neuron-specific voltage-dependent K+ current with a well established role in the control of neuronal excitability. In this study, by means of a combined biochemical, pharmacological, and electrophysiological approach, the role of presynaptic IKM in the release of previously taken up tritiated norepineprine (NE), GABA, and D-aspartate (D-ASP) from hippocampal nerve terminals (synaptosomes) has been evaluated. Retigabine (RT) (0.01-30 μM), a specific activator of IKM, inhibited [3H]NE, [ 3H]D-ASP, and [3H]GABA release evoked by 9 mM extracellular K+ ([K+]e). RT-induced inhibition of [3H]NE release was prevented by synaptosomal entrapment of polyclonal antibodies directed against KCNQ2 subunits, an effect that was abolished by antibody preabsorption with the KCNQ2 immunizing peptide; antibodies against KCNQ3 subunits were ineffective. Flupirtine (FP), a structural analog of RT, also inhibited 9 mM [K+] e-induced [3H]NE release, although its maximal inhibition was lower than that of RT. Electrophysiological studies in KCNQ2-transfected Chinese hamster ovary cells revealed that RT and FP (10 μM) caused a - 19 and -9 mV hyperpolarizing shift, respectively, in the voltage dependence of activation of KCNQ2 K+ channels. In the same cells, the cognition enhancer 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991) (10 μM) blocked KCNQ2 channels and prevented their activation by RT (1-10 μM). Finally, both XE-991 (10-100 μM) and tetraethylammonium ions (100 μM) abolished the inhibitory effect of RT (1 μM) on [3H]NE release. These findings provide novel evidence for a major regulatory role of KCNQ2 K+ channel subunits in neurotransmitter release from rat hippocampal nerve endings.

Original languageEnglish
Pages (from-to)592-597
Number of pages6
JournalJournal of Neuroscience
Issue number3
Publication statusPublished - Jan 21 2004


  • Epilepsy
  • Hippocampus
  • KCNQ2 subunits
  • Norepinephrine release
  • Potassium channels
  • Retigabine

ASJC Scopus subject areas

  • Neuroscience(all)


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